The objective of the research presented in this proposal is to determine the functional significance and the underlying mechanisms of action potential conduction block in the nervous system. This entails investigation of the behavioral manifestations, the ionic mechanisms and the metabolic processes of action potential propagation block. Action potential discharge recorded in intact animals will be used to trigger nerve stimulation in dissected preparations. Using focal extracellular recordings of action potentials, the occurrence and the location of propagation failure will be registered. By recording simultaneously from axon branches which innervate target cells with different functional roles the behavioral consequences of the location at which conduction blocks occur will be determined. The magnitude and the time course of changes in the intracellular ionic activities of potassium and sodium during block development will be monitored using K ion and Na ion-selective microelectrodes. Concentration changes in fine nerve terminals will be determined by means of electron probe analysis; the characteristic x-rays emitted by Na ion and K ion in response to a scanning electron beam in a region of conduction failure will be measured. To determine if depletion of the high-energy phosphates ATP and phosphoarginine are associated with conduction block, their concentrations in regions where propagation failure occurs will be assayed fluorometrically using enzyme cycling techniques to enhance sensitivity.